Variable shortening of AV delay for treatment of cardiac disease

ABSTRACT

An implantable pacing device for delivering ventricular pacing may be configured to intermittently and variably reduce the AV delay interval used in an atrial triggered pacing mode in a manner that simulates exercise. The device may be programmed to intermittently switch to and from a variably shortened AV delay mode according to defined entry and exit conditions.

RELATED APPLICATIONS

This application is related to co-pending U.S. patent application Ser.Nos. 11/615,383 and 11/559,131 (Attorney Docket Nos. 279.C11US1 and279.A67US1), the disclosures of which are hereby incorporated byreference.

FIELD OF THE INVENTION

This invention pertains to apparatus and methods for the treatment ofheart disease and to devices providing electrostimulation to the heartsuch as cardiac pacemakers.

BACKGROUND

Heart failure (HF) is a debilitating disease that refers to a clinicalsyndrome in which an abnormality of cardiac function causes a belownormal cardiac output that can fall below a level adequate to meet themetabolic demand of peripheral tissues. Heart failure can be due to avariety of etiologies with ischemic heart disease being the most common.Inadequate pumping of blood into the arterial system by the heart issometimes referred to as “forward failure,” with “backward failure”referring to the resulting elevated pressures in the lungs and systemicveins which lead to congestion. Backward failure is the naturalconsequence of forward failure as blood in the pulmonary and venoussystems fails to be pumped out. Forward failure can be caused byimpaired contractility of the ventricles due, for example, to coronaryartery disease, or by an increased afterload (i.e., the forces resistingejection of blood) due to, for example, systemic hypertension orvalvular dysfunction. One physiological compensatory mechanism that actsto increase cardiac output is due to backward failure which increasesthe diastolic filling pressure of the ventricles and thereby increasesthe preload (i.e., the degree to which the ventricles are stretched bythe volume of blood in the ventricles at the end of diastole). Anincrease in preload causes an increase in stroke volume during systole,a phenomena known as the Frank-Starling principle. Thus, heart failurecan be at least partially compensated by this mechanism but at theexpense of possible pulmonary and/or systemic congestion.

When the ventricles are stretched due to the increased preload over aperiod of time, the ventricles become dilated. The enlargement of theventricular volume causes increased ventricular wall stress at a givensystolic pressure. Along with the increased pressure-volume work done bythe ventricle, this acts as a stimulus for hypertrophy of theventricular myocardium which leads to alterations in cellular structure,a process referred to as ventricular remodeling. Ventricular remodelingleads to further dysfunction by decreasing the compliance of theventricles (thereby increasing diastolic filling pressure to result ineven more congestion) and causing eventual wall thinning that causesfurther deterioration in cardiac function. It has been shown that theextent of ventricular remodeling is positively correlated with increasedmortality in HF patients.

A myocardial infarction (MI) is the irreversible damage done to asegment of heart muscle by ischemia, where the myocardium is deprived ofadequate oxygen and metabolite removal due to an interruption in bloodsupply. It is usually due to a sudden thrombotic occlusion of a coronaryartery, commonly called a heart attack. If the coronary artery becomescompletely occluded and there is poor collateral blood flow to theaffected area, a transmural or full-wall thickness infarct can result inwhich much of the contractile function of the area is lost. Over aperiod of one to two months, the necrotic tissue heals, leaving a scar.The most extreme example of this is a ventricular aneurysm, where all ofthe muscle fibers in the area are destroyed and replaced by fibrous scartissue. Even if the ventricular dysfunction as a result of the infarctis not immediately life-threatening, a common sequela of a transmuralmyocardial infarction, or any major MI, especially in the leftventricle, is heart failure brought about by ventricular remodeling inresponse to the hemodynamic effects of the infarct that causes changesin the shape and size of the ventricle. The remodeling is initiated inresponse to a redistribution of cardiac stress and strain caused by theimpairment of contractile function in the infarcted area as well as innearby and/or interspersed viable myocardial tissue with lessenedcontractility due to the infarct. Following an MI, the infarcted areaincludes tissue undergoing ischemic necrosis and is surrounded by normalmyocardium. Until scar tissue forms and even after it forms, the areaaround the infarcted area is particularly vulnerable to the distendingforces within the ventricle and undergoes expansion over a period ofhours to days. Over the next few days and months after scar tissue hasformed, global remodeling and chamber enlargement occur due to complexalterations in the architecture of the ventricle involving bothinfarcted and non-infarcted areas. It has been found that the extent ofleft ventricular remodeling in the late period after an infarction, asrepresented by measurements of end-systolic and end-diastolic leftventricular volumes, is an even more powerful predictor of subsequentmortality than the extent of coronary artery disease.

Remodeling is thought to be the result of a complex interplay ofhemodynamic, neural, and hormonal factors that occur primarily inresponse to myocardial wall stress. As noted above, one physiologicalcompensatory mechanism that acts to increase cardiac output is increaseddiastolic filling pressure of the ventricles as an increased volume ofblood is left in the lungs and venous system, thus increasing preload.The ventricular dilation resulting from the increased preload causesincreased ventricular wall stress at a given systolic pressure inaccordance with Laplace's law. Along with the increased pressure-volumework done by the ventricle, this acts as a stimulus for compensatoryhypertrophy of the ventricular myocardium. Hypertrophy can increasesystolic pressures but, if the hypertrophy is not sufficient to meet theincreased wall stress, further and progressive dilation results. Thisnon-compensatory dilation causes wall thinning and further impairment inleft ventricular function. It also has been shown that the sustainedstresses causing hypertrophy may induce apoptosis (i.e., programmed celldeath) of cardiac muscle cells. Thus, although ventricular dilation andhypertrophy may at first be compensatory and increase cardiac output,the process ultimately results in further deterioration and dysfunction.

It has long been known that the heart muscle responds favorably toexercise so as to result in greater pumping efficacy. Studies have shownthat HF and post-MI patients can improve their cardiac function andprognosis with regular periods of exercise. Many HF and post-MIpatients, however, are either debilitated and cannot exercise or do nottolerate exercise well enough to exercise effectively.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the physical configuration of an exemplary pacingdevice.

FIG. 2 shows the components of an exemplary device.

FIG. 3 is a block diagram of the electronic circuitry of an exemplarydevice.

FIG. 4 shows the changes in AV delay as a device periodically enters andexits an AVD reduction mode.

FIG. 5 shows the changes in AV delay as a device periodically enters andexits a variably shortened AVD mode.

FIG. 6 illustrates an exemplary algorithm for controlling entry and exitinto the VSAVDR mode.

DETAILED DESCRIPTION

Clinical studies have shown that HF and post-MI patients who follow aregular (e.g. 20 min/day, 3 times a week) exercise regimen havesymptomatic improvement compared to those who are sedentary. However,not all HF and post-MI patients can exercise due to their cardiacdisease or other debilitating conditions. Described herein are methodsand devices that use short durations of pacing therapy designed to mimicexercise in order to provide protection from heart failure developmentand/or attenuation/reversal of cardiac disease progression.

When cardiac output is insufficient to meet the increased metabolicdemand, the body responds to the situation with increased activity ofthe sympathetic nervous system that, among other things, increases heartrate, myocardial contractility, and blood volume. Although acutelybeneficial, the long-term effects of increased sympathetic activity aredeleterious and lead to ventricular remodeling such as described above.A characteristic feature of chronic cardiac disease is an abnormalautonomic tone with an attenuated level of parasympathetic activityrelative to sympathetic activity. When the heart is stressed on aperiodic short-term basis, however, such as occurs with regularexercise, the effect is beneficial on both myocardial function andautonomic tone, leading to an increased level of parasympatheticactivity. In order to mimic the effects of exercise, pacing therapy canbe delivered on a short-term basis in a manner that stresses the heartsimilar to exercise. Such pacing therapy is referred to herein assimulated exercise pacing. Simulated exercise pacing may generallyinvolve pacing the heart in a manner that temporarily increases cardiacstress levels with or without compromising cardiac output by producingrelatively inefficient ventricular contractions and/or some degree ofatrio-ventricular dyssynchrony such as described in co-pending U.S.patent application Ser. No. 11/559,131.

In atrial triggered pacing modes (e.g., VDD and DDD modes), aventricular escape interval is defined between atrial and ventricularevents, referred to as the atrio-ventricular delay interval or AVD. TheAVD interval is triggered by an atrial sense or pace and stopped by aventricular sense or pace. A ventricular pacing pulse is delivered uponexpiration of the AVD interval if no ventricular sense occurs before.The value of the AVD interval for optimal preloading of the ventricleswill vary with heart rate and in a manner that differs from patient topatient. If a patient has a physiologically normal atrial rhythm,ventricular pacing triggered by atrial senses also allows theventricular pacing rate to be responsive to the metabolic needs of thebody. If the atrial rhythm is too slow, the device can be configured topace the atria on an inhibited demand basis such as in DDD mode whichmay include rate-adaptive pacing. An atrial escape interval is thendefined as the maximum time interval in which an atrial sense must bedetected after a ventricular sense or stimulus before an atrial stimuluswill be delivered. The lower rate limit interval is then the sum of theatrial escape interval and the AVD interval.

In a patient with normal AV conduction (i.e., no degree of AV block) andnormal ventricular function, the optimum AVD that maximizes cardiacoutput will usually correspond closely with the intrinsicatrio-ventricular interval. When such an AVD is used for normalbradycardia pacing of the ventricles, the ventricular pace is thusdelivered close to the time that the ventricles become excited due tointrinsic AV conduction. Similarly, an optimum AVD for resynchronizingthe ventricles with biventricular pacing in a patient with intact AVconduction will usually involve pre-exciting the ventricle having theconduction deficit with an AVD that causes that ventricle to contract atroughly the same time that the contralateral ventricle contracts due tointrinsic AV conduction. As described below, employing an AVD forventricular pacing that is shorter than the intrinsic atrio-ventricularinterval (or shorter than the normal intrinsic atrio-ventricularinterval in the case of a patient with AV block) is one way ofsimulating exercise.

Reduction of the AVD primarily results in two things: a reduction in theextent of ventricular pre-loading by the atria and a relativelyasynchronous ventricular contraction brought about by the ventriclesbeing excited from one or more ventricular pacing sites with little orno accompanying ventricular excitation via intrinsic AV conduction. Mostpatients respond negatively to AVD reduction with a relativelycompromised cardiac output due to the reduction in atrial preloadingand/or the relatively asynchronous and inefficient ventricularcontraction resulting from a pace without intrinsic excitation from AVconduction. Delivering ventricular pacing with a reduced AVD to anegatively responding patient produces a relatively asynchronous andinefficient contraction that simulates the stress effects of exercise onthe heart. The optimum value of a shortened AVD for producing anasynchronous contraction may vary from patient to patient but wouldtypically be between 10-80 percent of the intrinsic atrio-ventricularinterval. An implantable pacing device for delivering ventricular pacingmay be configured to intermittently reduce the AVD interval in order tosimulate exercise in patients with compromised ventricular function(e.g., HF patients and post-MI patients). The AVD interval may bereduced, referred to herein as an AVD reduction or AVDR mode, byshortening the AVD in an atrial triggered ventricular pacing mode or byswitching to a non-atrial triggered ventricular pacing mode (e.g., VVI)and delivering paces at a rate above the intrinsic rate.

It has also been found that the intrinsic atrio-ventricular intervalexhibits increased variability during normal exercise. In order to mimicthis aspect of normal exercise, the AVD can be variably shortened duringwhat may be called a variably shortened AVD mode or VSAVD mode.Ventricular pacing in a VSAVD mode may delivered on an intermittentbasis as controlled by specified entry and exit conditions that couldinclude lapsed time intervals, detection of pulmonary edema, exertionlevel (e.g., as measured by intrinsic heart rate, activity level, orminute ventilation), patient posture, cardiac output, circadian pattern,disordered breathing patterns (e.g., apnea), and blood pressure. A moredetailed description of these techniques is given below after adescription of an exemplary cardiac device.

1. EXEMPLARY CARDIAC DEVICE

FIG. 1 shows an implantable cardiac device 100 for delivering pacingtherapy. Implantable pacing devices are typically placed subcutaneouslyor submuscularly in a patient's chest with leads threaded intravenouslyinto the heart to connect the device to electrodes disposed within aheart chamber that are used for sensing and/or pacing of the chamber.Electrodes may also be positioned on the epicardium by various means. Aprogrammable electronic controller causes the pacing pulses to be outputin response to lapsed time intervals and/or sensed electrical activity(i.e., intrinsic heart beats not as a result of a pacing pulse). Thedevice senses intrinsic cardiac electrical activity through one or moresensing channels, each of which incorporates one or more of theelectrodes. In order to excite myocardial tissue in the absence of anintrinsic beat, pacing pulses with energy above a certain threshold aredelivered to one or more pacing sites through one or more pacingchannels, each of which incorporates one or more of the electrodes. FIG.1 shows the exemplary device having two leads 200 and 300, each of whichis a multi-polar (i.e., multi-electrode) lead having electrodes 201-203and 301-303, respectively. The electrodes 201-203 are disposed in theright ventricle in order to excite or sense right ventricular or septalregions, while the electrodes 301-303 are disposed in the coronary sinusin order to excite or sense regions of the left ventricle. Otherembodiments may use any number of electrodes in the form of unipolarand/or multi-polar leads in order to excite different myocardial sites.As explained below, once the device and leads are implanted, the pacingand/or sensing channels of the device may be configured with selectedones of the multiple electrodes in order to selectively pace or sense aparticular myocardial site(s).

FIG. 2 shows the components of the implantable device 100 in moredetail. The implantable device 100 includes a hermetically sealedhousing 130 that is placed subcutaneously or submuscularly in apatient's chest. The housing 130 may be formed from a conductive metal,such as titanium, and may serve as an electrode for deliveringelectrical stimulation or sensing in a unipolar configuration. A header140, which may be formed of an insulating material, is mounted on thehousing 130 for receiving leads 200 and 300 which may be thenelectrically connected to pulse generation circuitry and/or sensingcircuitry. Contained within the housing 130 is the electronic circuitry132 for providing the functionality to the device as described hereinwhich may include a power supply, sensing circuitry, pulse generationcircuitry, a programmable electronic controller for controlling theoperation of the device, and a telemetry transceiver capable ofcommunicating with an external programmer or a remote monitoring device.

FIG. 3 shows a system diagram of the electronic circuitry 132. A battery22 supplies power to the circuitry. The controller 10 controls theoverall operation of the device in accordance with programmedinstructions and/or circuit configurations. The controller may beimplemented as a microprocessor-based controller and include amicroprocessor and memory for data and program storage, implemented withdedicated hardware components such as ASICs (e.g., finite statemachines), or implemented as a combination thereof. The controller alsoincludes timing circuitry such as external clocks for implementingtimers used to measure lapsed intervals and schedule events. As the termis used herein, the programming of the controller refers to either codeexecuted by a microprocessor or to specific configurations of hardwarecomponents for performing particular functions. Interfaced to thecontroller are sensing circuitry 30 and pulse generation circuitry 20 bywhich the controller interprets sensing signals and controls thedelivery of paces in accordance with a pacing mode. The controller iscapable of operating the device in a number of programmed pacing modeswhich define how pulses are output in response to sensed events andexpiration of time intervals. The controller also implements timersderived from external clock signals in order to keep track of time andimplement real-time operations such as scheduled AVDR or VSAVD modepacing.

The sensing circuitry 30 receives atrial and/or ventricular electrogramsignals from sensing electrodes and includes sensing amplifiers,analog-to-digital converters for digitizing sensing signal inputs fromthe sensing amplifiers, and registers that can be written to foradjusting the gain and threshold values of the sensing amplifiers. Thesensing circuitry of the pacemaker detects a chamber sense, either anatrial sense or ventricular sense, when an electrogram signal (i.e., avoltage sensed by an electrode representing cardiac electrical activity)generated by a particular channel exceeds a specified detectionthreshold. Pacing algorithms used in particular pacing modes employ suchsenses to trigger or inhibit pacing, and the intrinsic atrial and/orventricular rates can be detected by measuring the time intervalsbetween atrial and ventricular senses, respectively.

The pulse generation circuitry 20 delivers pacing pulses to pacingelectrodes disposed in the heart and includes capacitive discharge orcurrent source pulse generators, registers for controlling the pulsegenerators, and registers for adjusting pacing parameters such as pulseenergy (e.g., pulse amplitude and width). The device allows adjustmentof the pacing pulse energy in order to ensure capture of myocardialtissue (i.e., initiating of a propagating action potential) by a pacingpulse. The pulse generation circuitry may also include a shocking pulsegenerator for delivering a defibrillation/cardioversion shock via ashock electrode upon detection of a tachyarrhythmia.

A telemetry transceiver 80 is interfaced to the controller which enablesthe controller to communicate with an external device such as anexternal programmer and/or a remote monitoring unit. An externalprogrammer is a computerized device with an associated display and inputmeans that can interrogate the pacemaker and receive stored data as wellas directly adjust the operating parameters of the pacemaker. Theexternal device may also be a remote monitoring unit that may beinterfaced to a patient management network enabling the implantabledevice to transmit data and alarm messages to clinical personnel overthe network as well as be programmed remotely. The network connectionbetween the external device and the patient management network may beimplemented by, for example, an internet connection, over a phone line,or via a cellular wireless link. A switch 24 is also shown as interfacedto the controller in this embodiment to allow the patient to signalcertain conditions or events to the implantable device. In differentembodiments, the switch 24 may be actuated magnetically, tactilely, orvia telemetry such as by a hand-held communicator. The controller may beprogrammed to use actuation of the switch 24 to control the delivery ofAVDR or VSAVD mode pacing.

A pacing channel is made up of a pulse generator connected to anelectrode, while a sensing channel is made up of a sense amplifierconnected to an electrode. Shown in the figure are electrodes 40 ₁through 40 _(N) where N is some integer. The electrodes may be on thesame or different leads and are electrically connected to a MOS switchmatrix 70. The switch matrix 70 is controlled by the controller and isused to switch selected electrodes to the input of a sense amplifier orto the output of a pulse generator in order to configure a sensing orpacing channel, respectively. The device may be equipped with any numberof pulse generators, amplifiers, and electrodes that may be combinedarbitrarily to form sensing or pacing channels. The device is thereforecapable of delivering single-site or multiple site ventricular pacingfor purposes of exercise simulation as well as conventional pacing. Oneor more pacing channels may also be configured, by appropriate leadplacement and pulse energy/frequency settings, for delivering electricalstimulation to stimulate sympathetic and/or parasympathetic nerves. Forexample, a lead with a stimulation electrode may be placed in proximityto the vagus nerve in order to stimulate that nerve and increaseparasympathetic activity. The switch matrix 70 also allows selected onesof the available implanted electrodes to be incorporated into sensingand/or pacing channels in either unipolar or bipolar configurations. Abipolar sensing or pacing configuration refers to the sensing of apotential or output of a pacing pulse between two closely spacedelectrodes, where the two electrodes are usually on the same lead (e.g.,a ring and tip electrode of a bipolar lead or two selected electrodes ofa multi-polar lead). A unipolar sensing or pacing configuration is wherethe potential sensed or the pacing pulse output by an electrode isreferenced to the conductive device housing or another distantelectrode.

The device may also include one or more physiological sensing modalitiesfor use in controlling pacing and/or the initiation/cessation of theAVDR or VSAVD mode. An accelerometer 26 enables the controller to adaptthe pacing rate in accordance with changes in the patient's physicalactivity. In order to detect patient posture for purposes of controllingAVDR or VSAVD mode pacing, the accelerometer 26 may be a multi-axisaccelerometer. An impedance sensor 25 may be configured with electrodesfor measuring minute ventilation for use in rate adaptive pacing and/orcardiac output for use in controlling the AVDR or VSAVD mode. Theimpedance sensor 25 may also be configured to detect pulmonary edema bymeasurement of trans-pulmonary impedance. The device may also include apressure sensor that may be used, for example, to measure pressure inthe pulmonary artery. An accelerometer or acoustic sensor may be used asa heart sound sensor to detect heart sounds.

2. REDUCTION OF AVD TO SIMULATE EXERCISE

One way of delivering simulated exercise pacing is with an AVDR or VSAVDmode. As described earlier, reducing the AVD causes AV dyssynchrony thatdecreases the amount of ventricular preloading. Decreasing theventricular preload can decrease cardiac output, and the body mayrespond to this decrease in a manner similar to its response toexercise. Ventricular pacing with a reduced AVD also causes a relativelyasynchronous contraction that can decrease cardiac output to mimic theeffects of exercise. The mechanism behind this effect is that when theventricles are stimulated to contract by a pacing pulse applied throughan electrode located at a particular pacing site, the excitation spreadsfrom the pacing site by conduction through the myocardium. This isdifferent from the normal physiological situation, where the spread ofexcitation to the ventricles from the AV node makes use of the heart'sspecialized conduction system made up of Purkinje fibers which allows arapid and synchronous excitation of the entire ventricular myocardium.The excitation resulting from a pacing pulse, on the other hand,produces a relatively asynchronous contraction due to the slowervelocity at which the excitation is conducted from the pacing site tothe rest of the myocardium. Regions of the myocardium located moredistally from the pacing site are also excited later than regionsproximal to the pacing site as compared with an intrinsic contractionand subjected to increased mechanical stress. This increased regionalstress may elicit cellular changes in the myocardium similar to thosecaused by stress due to exercise.

As noted above, it has been found that the intrinsic atrio-ventricularinterval (PR interval) exhibits increased variability during normalexercise. Such variability in the PR interval tends to counteractvariability in the RR interval. In order to more closely duplicate thephysiology of normal exercise with simulated exercise pacing, the AVDmay be variably shortened in a VSAVD mode. FIGS. 4 and 5 illustrate thedifferences between an AVDR mode and a VSAVD mode. FIG. 4 shows the timecourse of changes in AV delay as a device periodically enters and exitsan AVD reduction mode, while FIG. 5 shows the time course of changes inAV delay as a device periodically enters and exits a VSAVD mode. In anAVDR mode, the AVD is shortened to some value below the normal AVD whereit remains until the mode is exited. In the VSAVD mode, the AVD isshortened to a range of values below the normal AVD, referred to as thereduced AVD range, and the AVD is made to vary within the reduced AVDrange while the mode is operative. In the case of a patient with AVblock, the AV delay may be made to vary within a range selected from avalue shorter than a nominal intrinsic AV delay interval based upondemographic data or a value shorter than a nominal intrinsic AV delayinterval based upon hemodynamic measurements. In specific embodiments,the AV delay is made to vary within a range that is 10-80% of thepatient's measured intrinsic AV delay interval, 10-80% of a nominalintrinsic AV delay interval based upon demographic data, or 10-80% of anominal intrinsic AV delay interval based upon hemodynamic measurements.The variation of the AVD during the VSAVD mode may be implemented in anumber of different ways. For example, the AVD may be made to varyaccording to a predetermined sequence of values within the reduced AVDrange or according to a pseudo-random sequence of values within thereduced AVD range. Either instead of, or in addition to such prescribedvariation, the AVD may be made to vary according to measured parametersthat trigger variation of the AVD where the AVD may or may not beconstrained to remain within the reduced AVD range. Examples of suchtriggering parameters include previous PP intervals (i.e., the intervalsbetween atrial senses), previous RR intervals (i.e., the intervalsbetween ventricular senses), measured heart rate variability, patientposture, respiratory inspiration and expiration as detected by a minuteventilation sensor, and hemodynamic parameters such as blood pressure orcardiac stroke volume as measured by an impedance sensor. In the case ofrespiratory variation, for example, the AVD could be shortened withinspiration and lengthened with expiration.

VSAVD pacing can be delivered to the heart in a way that mimics thebeneficial effects of exercise. Chronic simulated exercise pacing,however, could overstress the heart in HF or post-MI patients and couldbe hazardous. Accordingly, it would ordinarily be preferable to deliversimulated exercise pacing on an intermittent basis. As described below,a pacing device may therefore be configured to switch from a normaloperating mode to an VSAVD mode according to some defined exit and entryconditions that cause intermittent operation in the VSAVD mode. Suchentry and exit conditions, for example, may define a schedule thatspecifies switching in response to lapsed time intervals and/or inresponse to one or more other types of conditions detectable by thedevice.

3. IMPLEMENTATION OF NORMAL AND VSAVD MODES

As defined herein, the VSAVD mode is an atrial triggered ventricularpacing mode (e.g., VDD, DDD, or DDDR) in which ventricular pacing isdelivered with a variably shortened AVD. Switching from a normaloperating mode to the VSAVD mode may be implemented in a number of ways.If the normal mode does not include delivery of pacing therapy, theVSAVD mode may include delivery of ventricular pacing in an atrialtriggered mode with a short and variable AVD. If the normal modeincludes atrial triggered pacing with a specified AVD, the VSAVD modemay include ventricular pacing in an atrial triggered mode using an AVDshorter than that used in the normal operating mode and made to vary asdescribed above. For purposes of specifying the reduced AVD range usedin the VSAVD mode, the device may be configured to measure the intrinsicatrio-ventricular interval and compute the AVD as a specified percentagethereof. For patients with AV block whose intrinsic atrio-ventricularinterval cannot be measured, a reduced AVD may be calculated as apercentage of a nominal intrinsic atrio-ventricular interval. Thenominal intrinsic atrio-ventricular interval may be based, for example,upon demographic data reflecting a normal atrio-ventricular interval orbased upon individualized value determined from hemodynamic measurementsof a particular patient while pacing with different AVD values. Whensome kind of pacing therapy is delivered in the normal operating modeand the device possesses multiple pacing channels with different pacingsites, the VSAVD mode may involve using either the same or a differentpacing channel for delivering ventricular pacing. The VSAVD mode mayalso involve ventricular pacing at multiple sites and/or switching todifferent pacing sites during operation of the mode according to somedefined schedule.

4. CONDITIONAL ENTRY AND EXIT INTO VSAVD MODE

The device may be configured to use one or more entry and/or exitconditions in controlling entry and/or exit into the VSAVD mode. Anentry or exit condition could be, for example, a lapsed time interval(e.g., specified time(s) of the day), actuation of a switch by thepatient (e.g., a magnetically or tactilely actuated switch interfaced tothe device controller), a command received via telemetry, detection ornon-detection of a condition such as pulmonary edema or a supineposture, or a measured variable being within or out of a specifiedrange. Examples of such measured variables include heart rate, activitylevel, minute ventilation, cardiac output, heart sounds, and bloodpressure. Entry and/or exit conditions may also be composite conditionswhere a plurality of entry and/or exit conditions are logically ORed orANDed together to determine whether a composite entry or entry conditionis satisfied. FIG. 6 illustrates an exemplary algorithm executable bythe device controller for controlling entry and exit into the VSAVDmode. The controller is also programmed to vary the AVD in the mannersdescribed above while in the VSAVD mode. In this example, one of theentry conditions is a specified time of the day during which it isdesired to delivery VSAVD pacing if other entry conditions are met. Asshown in the figure, the controller of the device is programmed totransition through a number of different states, designated as A1through A6. At state A1, the device operates in its normal operatingmode. At state A2, while continuing to operate in state A1, the devicedetermines whether it should switch to the VSAVD mode based upon alapsed time interval or a triggering condition. Optionally, the devicemay also be configured to test for one or more particular entryconditions before switching to the simulated exercise mode asimplemented by state A3. Examples of entry conditions that must besatisfied before the switch to the VSAVD mode include a measuredexertion level being within a specified entry range (where exertionlevel may be measured by, e.g., heart rate, activity level, or minuteventilation), non-detection of cardiac arrhythmias, non-detection ofcardiac ischemia, receipt of a telemetry command, and actuation by thepatient of a magnetically or tactilely actuated switch incorporated intothe device that allows switching to the VSAVD mode. At state A3, thedevice checks to see if the one or more entry conditions are satisfiedand returns to state A1 if not. If the appropriate entry conditions aresatisfied, the device switches to the VSAVD mode at state A4. The VSAVDmode supercedes the normal operating mode to the extent necessary tocarry out the VSAVD pacing but may allow certain functions performed inthe normal operating mode to continue. Alternatively, the VSAVD modecould be said to incorporate particular functions of the normaloperating mode, which functions are modified if necessary to deliver theVSAVD pacing. While executing in the VSAVD mode, the device may beconfigured to monitor for one or more exit conditions which cause thedevice to revert to the normal operating mode. Such exit conditionscould be the same or different from the entry conditions that must besatisfied before entering the VSAVD mode. At state A5, while executingin the VSAVD mode, the device monitors for the occurrence of one or moreexit conditions such as a measured exertion level being outside aspecified permissible range, a measured heart rate being outside aspecified permissible range, presence of a cardiac arrhythmia, presenceof cardiac ischemia, receipt of a telemetry command, and actuation bythe patient of a magnetically or tactilely actuated switch incorporatedinto the device by the patient to stop delivery of VSAVD pacing. If anexit condition occurs, the device returns to the normal operating modeat state A1. Otherwise, the device proceeds to state A6 and checks tosee if the prescribed amount and/or duration of VSAVD pacing have beendelivered. If the specified amount or duration of VSAVD pacing has beendelivered, the device returns to state A1 and resumes the normaloperating mode. Otherwise, the device loops back to state A5 to monitorfor exit conditions. For example, the device may be programmed todeliver VSAVD pacing that simulates exercise for a prescribed amount oftime per day (e.g. 30 min). The time when therapy delivery is startedmay be random (once per day at a random time), at a specific time eachday, or triggered by a specific event (e.g. when the patient fallsasleep, the patient wakes up, or the patient's exertion level fallsbelow a certain threshold).

5. EXEMPLARY IMPLEMENTATION SCHEMES

In an exemplary embodiment, the device is programmed to periodically(e.g., every 24 to 72 hours) switch to the VSAVD mode for some specifiedperiod of time, referred to as the AVD reduction period or AVDRP (e.g.,15-60 minutes). If the device delivers some kind of therapy during itsnormal mode (e.g., for cardiac resynchronization therapy, remodelingcontrol therapy, or bradycardia), the VSAVD mode could be implemented asatrial triggered ventricular pacing (e.g., VDD or DDD) with a shorter AVdelay than that used in the normal mode that also varies during theAVDRP. If no pacing is delivered in the normal mode, the AVDR mode couldbe implemented as atrial triggered ventricular pacing with a specifiedshort and variable AV delay. If the device is equipped with an atriallead and only a single implanted ventricular lead, the implantedventricular site would be paced with the reduced and variable AV delayfor the entire AVDRP. If the device is equipped with electrodesimplanted at multiple ventricular sites (e.g., as multiple leads or asone or multi-polar leads), all or some selected subset of theventricular pacing sites could be paced during the AVDRP. Theventricular sites could also be rotated during the AVDRP according to aspecified duty cycle. For example, if the device has electrodesimplanted at two ventricular sites, the AVDR mode could be implementedas VSAVD pacing delivered to a selected one of the sites for entireAVDRP, VSAVD pacing delivered to one site for some percentage (e.g. 50%)of the AVDRP and switching to the other site for the remaining portionof the AVDRP, or VSAVD pacing delivered to both ventricular sites foreach paced cycle (either simultaneously or with offset between the twosites) during the entire AVDRP. Similarly, if the device has more thantwo ventricular leads or more than two ventricular pacing sites (e.g.quadripolar lead), VSAVD pacing could be delivered to a single selectedsite for the entire AVDRP, VSAVD pacing could be delivered to all of theimplanted sites for each paced cycle (either simultaneously or withspecified offsets) during the AVDRP, or VSAVD pacing could be rotatedfrom one ventricular site to the next during the AVDRP. For example, ifthere are four ventricular pacing sites, VSAVD pacing could be deliveredto a first site for the first 25% of the AVDRP, to a second site for thenext 25% of the AVDRP, etc., where the percentage of time each site ispaced may or may not be evenly distributed.

6. OTHER EMBODIMENTS

As described above, VSAVD pacing may be used to simulate exercise byintentionally causing asynchronous ventricular contractions. Asdescribed in co-pending U.S. patent application Ser. No. 11/559,131,asynchronous contractions may also be produced in other ways such as bypacing different sites at different times to cause the heart to contractin an inefficient way, and the embodiments described herein may becombined with any of the embodiments described in that application.

The invention has been described in conjunction with the foregoingspecific embodiments. It should be appreciated that those embodimentsmay also be combined in any manner considered to be advantageous. Also,many alternatives, variations, and modifications will be apparent tothose of ordinary skill in the art. Other such alternatives, variations,and modifications are intended to fall within the scope of the followingappended claims.

1. A cardiac device, comprising: one or more ventricular pacing channelsfor delivering pacing pulses to one or more ventricular sites; an atrialsensing channel; a controller programmed to operate the device in eithera normal operating mode or variably shortened AV delay (VSAVD) mode;wherein, in the VSAVD mode, the controller is programmed to deliverpaces to the one or more ventricular sites using an atrial triggeredpacing mode that decreases atrial preloading of the ventricles ascompared with the normal operating mode using an AV delay that variesduring the VSAVD mode; and, wherein the controller is programmed tointermittently switch from the normal operating mode to the VSAVD modeaccording to a one or more specified entry conditions and switch fromthe VSAVD mode to the normal operating mode according to one or morespecified exit conditions.
 2. The device of claim 1 wherein the VSAVDmode includes pacing a ventricular site using an atrial triggered pacingmode with an AV delay made to vary within a range selected from a valueshorter than a patient's measured intrinsic AV delay interval, a valueshorter than a nominal intrinsic AV delay interval based upondemographic data, or a value shorter than a nominal intrinsic AV delayinterval based upon hemodynamic measurements.
 3. The device of claim 2wherein the range is 10-80% of a value selected from the patient'smeasured intrinsic AV delay interval, a nominal intrinsic AV delayinterval based upon demographic data, or a nominal intrinsic AV delayinterval based upon hemodynamic measurements.
 4. The device of claim 1wherein the controller is programmed to vary the AV delay during theVSAVD mode according to a predetermined sequence of values.
 5. Thedevice of claim 1 wherein the controller is programmed to vary the AVdelay during the VSAVD mode according to a pseudo-random sequence ofvalues.
 6. The device of claim 1 wherein the controller is programmed tovary the AV delay during the VSAVD mode according to one or moremeasured triggering parameters that trigger variation of the AV delay.7. The device of claim 6 wherein the AV delay is constrained to remainwithin a reduced AV delay range while made to vary during the VSAVDmode.
 8. The device of claim 6 wherein the one or more measuredtriggering parameters may be selected from previous PP intervals,previous RR intervals, measured heart rate variability, patient postureas detected by an accelerometer, respiratory inspiration and expirationas detected by a minute ventilation sensor, blood pressure, heartsounds, and cardiac stroke volume as measured by an impedance sensor. 9.The device of claim 6 further comprising a respiratory sensor andwherein, during the VSAVD mode, the controller is programmed to shortenthe AV delay with inspiration and lengthen the AV delay with expiration.10. The device of claim 1 wherein the controller is programmed to usedifferent pacing channels in the VSAVD mode than in the normal operatingmode.
 11. A method for operating a cardiac pacing device, comprising:delivering pacing pulses to one or more ventricular sites in an atrialtriggered pacing mode with an AV delay; operating the device in either anormal operating mode or variably shortened AV delay (VSAVD) mode; inthe VSAVD mode, delivering paces to the one or more ventricular sitesusing an atrial triggered pacing mode that decreases atrial preloadingof the ventricles as compared with the normal operating mode using an AVdelay that varies during the VSAVD mode; and, intermittently switchingfrom the normal operating mode to the VSAVD mode according to a one ormore specified entry conditions and switching from the VSAVD mode to thenormal operating mode according to one or more specified exitconditions.
 12. The method of claim 11 wherein the VSAVD mode includespacing a ventricular site using an atrial triggered pacing mode with anAV delay made to vary within a range selected from a value shorter thana patient's measured intrinsic AV delay interval, a value shorter than anominal intrinsic AV delay interval based upon demographic data, or avalue shorter than a nominal intrinsic AV delay interval based uponhemodynamic measurements.
 13. The method of claim 12 wherein the rangeis 10-80% of a value selected from the patient's measured intrinsic AVdelay interval, a nominal intrinsic AV delay interval based upondemographic data, or a nominal intrinsic AV delay interval based uponhemodynamic measurements.
 14. The method of claim 11 further comprisingvarying the AV delay during the VSAVD mode according to a predeterminedsequence of values.
 15. The method of claim 11 further comprisingvarying the AV delay during the VSAVD mode according to a pseudo-randomsequence of values.
 16. The method of claim 11 further comprisingvarying the AV delay during the VSAVD mode according to one or moremeasured triggering parameters that trigger variation of the AV delay.17. The method of claim 16 wherein the AV delay is constrained to remainwithin a reduced AV delay range while made to vary during the VSAVDmode.
 18. The method of claim 16 wherein the one or more measuredtriggering parameters may be selected from previous PP intervals,previous RR intervals, measured heart rate variability, patient postureas detected by an accelerometer, respiratory inspiration and expirationas detected by a minute ventilation sensor, blood pressure, heartsounds, and cardiac stroke volume as measured by an impedance sensor.19. The method of claim 16 further comprising, during the VSAVD mode,shortening the AV delay with inspiration and lengthening the AV delaywith expiration.
 20. The method of claim 11 further comprising usingdifferent pacing channels in the VSAVD mode than in the normal operatingmode.